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阿加曲班治疗急性冠状动脉综合征的药代动力学评价。

Pharmacokinetic evaluation of argatroban for the treatment of acute coronary syndrome.

机构信息

University Hospital of Salamanca, Cardiology Division, Paseo San Vicente 58-182, 37007, Salamanca, Spain.

出版信息

Expert Opin Drug Metab Toxicol. 2012 Nov;8(11):1483-93. doi: 10.1517/17425255.2012.722621. Epub 2012 Sep 13.

Abstract

INTRODUCTION

Limitations and contraindications of heparins and oral vitamin K antagonists have led to the development of new anticoagulant drugs over the last few years. Argatroban is an intravenous direct thrombin inhibitor currently indicated for the prophylaxis and treatment of thrombosis associated with heparin-induced thrombocytopenia (HIT) and for patients at risk of HIT undergoing percutaneous coronary intervention (PCI). The role of argatroban for the treatment of acute coronary syndrome (ACS) is under evaluation.

AREAS COVERED

This article reviews the potential use of argatroban for the treatment of ACS and presents the pharmacokinetic data currently available. The authors also present the pharmacodynamic literature of agratroban in addition to highlighting the safety and tolerability of the drug.

EXPERT OPINION

Theoretically, argatroban's pharmacokinetics makes it an attractive alternative to heparin. Pharmacological advantages of argatroban over heparin include a more-predictable anticoagulant response and the absence of a risk of HIT. Furthermore, argatroban has a fast and predictable dose-dependent anticoagulant effect with low inter-individual variability. It is non-immugenic, not susceptible to degradation by proteases and it is cleared via the liver. These characteristics confer argotroban a different profile from other anticoagulants. Agatroban is an effective alternative for patients when heparin, lepirudin and bivalirudin cannot be used. Its utility in ACS and PCI in non-HIT patients has been evaluated but further studies are warranted to define its role in this context.

摘要

简介

肝素和口服维生素 K 拮抗剂的局限性和禁忌症促使近年来开发了新的抗凝药物。阿加曲班是一种静脉内直接凝血酶抑制剂,目前用于预防和治疗肝素诱导的血小板减少症(HIT)相关血栓形成,以及有发生 HIT 风险的接受经皮冠状动脉介入治疗(PCI)的患者。阿加曲班在急性冠状动脉综合征(ACS)治疗中的作用正在评估中。

涵盖领域

本文回顾了阿加曲班在 ACS 治疗中的潜在用途,并介绍了目前可用的药代动力学数据。作者还介绍了阿加曲班的药效学文献,同时强调了该药物的安全性和耐受性。

专家意见

从理论上讲,阿加曲班的药代动力学使其成为肝素的一种有吸引力的替代品。与肝素相比,阿加曲班具有药理学优势,包括更可预测的抗凝反应和不存在发生 HIT 的风险。此外,阿加曲班具有快速和可预测的剂量依赖性抗凝作用,个体间变异性低。它是非免疫原性的,不易被蛋白酶降解,通过肝脏清除。这些特性使阿加曲班与其他抗凝剂具有不同的特性。当肝素、来匹卢定和比伐卢定不能使用时,阿加曲班是患者的有效替代药物。已评估其在非 HIT 患者中的 ACS 和 PCI 中的应用,但需要进一步研究来确定其在该情况下的作用。

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